EFFECTS OF 2-DEOXY-D-GLUCOSE 387 



uptake of 2-DG being depressed progressively as the glucose concentration 

 is increased in rat diaphragm (Nakada and Wick, 1956; Kipnis, 1958) 

 and lymph node cells (Helmreich and Eisen, 1959). Nakada and Wick 

 (1956) showed that insulin can double the rate of 2-DG uptake by dia- 

 phragm, and Kipnis and Cori (1959, 1960) studied this in greater detail. In 

 normal diaphragm the 2-DG taken up appears as 2-deoxy-D-glucose-6-phos- 

 phate (2-DG-6-P), the rate of phosphorylation being apparently greater 

 than the rate of penetration. Diabetic diaphragm takes up and phosphory- 

 lates 2-DG at a reduced rate but 2-DG does not accumulate in the cells, 

 indicating the penetration is still rate-limiting. Addition of insulin acceler- 

 ates the uptake and some free 2-DG appears in the cells so that the phos- 

 phorylation is not increased proportionately. Epinephrine does not in- 

 fluence the penetration but slows phosphorylation of 2-DG. Transport of 

 2-DG across the entire diaphragm is slow, being about one-fifth the rate 

 for glucose and one-twenty-fifth the rate for galactose (Ungar and Psy- 

 choyos, 1963). It is possible that it is trapped in the muscle as 2-DG-6-P 

 since insulin depresses the transfer. The uptake of 2-DG by yeast in glucose- 

 phosphate medium is 5-10 times faster aerobically than anaerobically; 

 when glucose is omitted the aerobic uptake of 2-DG is not altered, but an- 

 aerobically there is a loss of 2-DG from the cells, so that the uptake is de- 

 pendent on aerobic processes and probably on the level of ATP since 2,4- 

 dinitrophenol acts like anaerobiosis (Kiesow, 1959). Certain fungi, such as 

 Neurospora crassa and Aspergillus oryzae, can grow with 2-DG as the sole 

 source of carbon (Sols et al., 1960 b) but not as rapidly as with glucose; 

 indeed, growth with glucose or other sugars is inhibited by 2-DG. E. coli 

 will not grow with 2-DG as the only carbon source and there is some evi- 

 dence that it does not penetrate into the cells (Gershanovich, 1963). The 

 evidence for the lack of entrance is that glycolysis is not inhibited in intact 

 cells where it is in extracts. 2-DG diffuses across the intestinal wall but is 

 not actively transported as are glucose, 1-DG, and 3-DG, indicating the 

 importance of the 2-position in transport (Wilson and Landau, 1960), 

 nor does 2-DG have an effect on the short-circuit current through the in- 

 testinal wall, such being associated with transport (Schultz and Zalusky, 

 1964; Barry et al, 1964). 



There is some information on the disposal of 2-DG in intact animals. 

 Injected into rabbits, it is rapidly distributed in the extracellular space 

 and some enters the tissues in eviscerated and nephrectomized animals, the 

 uptake being markedly stimulated by insulin (Wick et al., 1955). Since it 

 produces a block of glucose uptake for at least 8 hr, it is evident that little 

 2-DG is metabolized beyond the 2-DG-6-P stage in extrahepatic tissues. 

 This is confirmed by the finding that little or no C^^Oa is expired following 

 injection of 2-DG-Ci* (Wick et al, 1957). Blood levels of 2-DG are more 

 consistent after subcutaneous injection than when it is given intraperito- 



